CPAP and sleep disorders

Workshop CPAP and sleep disorders Fulvio Braido Allergy and Respiratory Diseases Department University of Genoa To explain better the pathophysiolo...
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Workshop

CPAP and sleep disorders Fulvio Braido Allergy and Respiratory Diseases Department University of Genoa

To explain better the pathophysiology of obstructive sleep apnea and its consequences

To emphasize the magnitude of the clinical problem To make familiar the practical aspects of the treatment techniques To identify unmet needs

Hystory of Sleep Breathing Disordes

Bickelmann AG, Burwell CS, Robin ED, Whaley RD.

Extreme obesity associated with alveolar hypoventilation. A pickwickian syndrome. Am J Med 1956; 21: 811-8.

OSA Mile Stones 1956 – Bickelmann AG, Burwell CS, Robin ED, Whaley RD. Extreme obesity associated with alveolar hypoventilation. A pickwickian syndrome. Am J Med 21: 8118. 1965 - Gastaut H, Tassinari CA, Duron B. Etude polygraphique des manifestations episodiques (hypniques et respiratoires) du syndrome de Pickwick. Rev Neural 112: 568-79. 1965 - Jung R, Kuhlo W. Neurophysiological studies of abnormal night sleep and the pickwickian syndrome. Prog Brain Res 18: 140-59. 1970 - Lugaresi E, Coccagna G, Mantovani M, Brignani F. Effets de la trachéotomie dans les hypersomnies avec respiration périodique. Rev Neurol 123: 267-8. 1972 - Lugaresi E. Organizer Symposium: Hypersomnia with Periodic Breathing. Rimini, Italy, May 25-27. Bull Physiopath Resp 8:967. 1981 - Sullivan CE, Issa FG, Berthon-Jones M, Eves L. Reversal of obstructive sleep apnoea by continuous positive airway pressure applied through the nares. Lancet i: 862-5.

OSA It is caracterized by repetitive collapse of the upper airways during sleep

Hpopnea: reduction in the airflow > 30% SO2 decrease > 3% at least 10 second

Apnoea: reduction in the airflow > 90% for at least 90% of the event at least 10 second

No inspiratory effort

Obstructive Sleep Apnea (OSA) • Snoring • Recurrent episodes of upper airway obstruction during sleep (apneas, hypopneas) • Arousals • Excessive and disabling daytime sleepiness • OSA Syndrome – features of OSA on sleep study + symptoms of daytime sleepiness

OSA  OSAS

OSAS It is characterised by repetitive collapse of the upper airways during sleep

Pathophysiology of Obstructive Sleep Apnea (continued)

Physiologic • Decreased function of upper airway dilator muscles (more than 20 skeletal muscles normally involved) • Decreased pharyngeal dilator reflex response • Decreased chemoreceptor drive/central drive (mixed with central sleep apnea)

Impact of sleep on ventilation Fall in phrenic and hypoglossal activity Reduce response to hypercapnia and hypoxia Reduction in upper ariways protective reflexes

Minute ventlation fall (16%) PaCO2 increase 4-6 mmHg PaO2 decrease (So2 decrease 2%) Irregular breathing during light and fragmented sleep Upper airways caliber reduction

SLEEP

Cortical imputs

Chemoreceptor sensitivity

Respiratory motor neurones

Hypoventilation Hypoxemia Hypercapnia

Respiratory muscle contraction

Lung mechanics: Airflow resistance FRC V/Q relationships

Pathophysiology of Obstructive Sleep Apnea

Mechanical • Short, thick neck • Neck flexion, supine position • Nasal obstruction, congestion, polyps

Pathophysiology of Obstructive Sleep Apnea (continued)

Anatomic • Enlarged tonsils and adenoids (esp. ages 3-5), enlarged uvula • Macroglossia • Retrognathia, craniofacial abnormalities • Compliant (floppy) pharynx, especially soft palate • Fat deposition in lateral walls of pharynx, pharyngeal dilator muscles (obesity) • Submucosal edema in lateral walls of pharynx

OSA pathophysiology Upper airway volume Pharyngeal collapsibility UA muscle activity Loss of UA protective reflex? Instability of the control of breathing ? Alteration of chemosensitivity?

Craniofacial size and Obesity can infuence upper airway caliber.

Watanabe et al, AJRCCM 165:260, 2002

Axial Upper Airway MR Images

Normal Subject

Apneic Patient

Subjects with OSA have smaller upper airway in wakefulness

OSA Patients Have Elevated Activity of Their Genioglossus Muscle During Wakefulness (Lost during sleep)

Mezzanotte et al, JCI 89:1571, 1992

Altered Upper Airway Dilator Muscle in English Bulldog

Chronic load and altered pattern of usage induce myopathic changes and following impaired ability to maintain pharyngeal patency

Petrof et al, J Appl Physiol 76:1746, 1994

Eupneic Inspiration (Revised from Fig. 2-1 in Levitzky’s Pulmonary Physiology)

Atmospheric Pressure : 0 cm H2O

Atmospheric Pressure : 0 cm H2O Flow in

No flow

Alveolar Alveolar pressure: pressure: 00 cm cm H H22O O

Inspiratory force

Outward recoil of chest wall Alveolar pressure: -1 cm H2O Inward recoil of alveoli

Intrapleural pressure: -5 cmH2O Transmural pressure= 0 cmH2O - (-5cmH2O)= +5 cmH2O

END EXPIRATION

Intrapleural pressure: -8 cmH2O Transmural pressure= -1 cmH2O - (-8cmH2O)= +7 cmH2O

DURING INSPIRATION

Forced Inspiration Atmospheric Pressure : 0 cm H2O

Atmospheric Pressure : 0 cm H2O

Flow in

No flow

Alveolar Alveolar pressure: pressure: 00 cm O cm H H22O

Inspiratory force Outward recoil of chest wall Alveolar pressure: -23 cm H2O Inward recoil of alveoli

Intrapleural pressure: -5 cmH2O Transmural pressure= 0 cmH2O - (-5cmH2O)= +5 cmH2O

END EXPIRATION

Intrapleural pressure: -30 cmH2O

Transmural pressure= -23 cmH2O - (-30 cmH2O)= +7 cmH2O

DURING INSPIRATION

Evidence for risk factors Risk factors: strong evidence • obesity • snoring • male sex • middle age and older • craniofacial abnormalities Risk factors: some evidence • Menopause • Family member with OSAS • Smoking • Nasal congestion at night

Demographic pattern of occurance Snoring and sleepiness are the strongest predictor of OSA 60% of men and 40% women between ages 41-65 years abitually snore.Thus is diagnostic utility is limited. Inspiration Expiration

Demographic pattern of occurance Obesity is a very strong risk factor for OSA all measure of obesity - neck and waist girths, weight, skin folds predict OSA An increase of 1 Kg/m2 in BMI yelds an estimated 30% increased in the odds of developing OSA An increase (decrease) of 1 kg/m2 in BMI yields and estimated 9% increase (decrease) in AHI

male: female ratio for OSA prevalence is 2:1

Obstructive Sleep Apnea Upper airway anatomy

Sites of obstruction during sleep apnea Hard Palate

Tongue

Tongue

Hyoid bone Larynx

Soft Palate

Nasopharynx

Oropharynx Epiglottis

Laryngopharynx

Fat Is Deposited in Tongue in Obese Subjects

Nashi et al, Laryngoscope 117:1467, 2007

A Obese Mouse sleeping upright to protect his upper airway

The standing sleeping mouse

Brennick et al, AJRCCM 179:158, 2009)

OSA prevalence by age: Sleep Heart Health Study

Young T et al, Arch Intern Med 2002

By age 50 ys, incidence rates among men and women are similar

Cleveland Family Study: interaction of age with gender and BMI The effect of BMI deacreases with age and may be irrilevant in elderly

Tishler et al, JAMA 2003

Frequency ans severity of OSA in pre post menopausal women

Clinical Features •Loud snoring •Excessive daytime somnolence •Intellectual deterioration •Personality changing •Erectile disfunction •Nocturnal enuresis •Morning headaches Guilleminault, et al 1978 Sleep Apnea Syndrome

Explanation for Hypersomnolence or Excessive Daytime Sleepiness • Repeated arousals (may be hundreds per night) interfere with sleep architecture, especially rapid eye movement sleep • Abnormal sleep architecture leads to daytime somnolence, decreased attentiveness, blunted mentation, depression, personality changes

Description of Sleep Apnea Event • Upper airway Intermittent obstruction • Decreased alveolar ventilation • Decreased alveolar PO2 ; increased alveolar PCO2 • Decreased arterial PO2 ; increased arterial PCO2 • Stimulation of arterial and central chemoreceptors; • Arousal - Secondary hyperventilation

Effects of Breathhold on Arterial PO2 and PCO2

Arterial Partial Pressure (mmHg)

100

O2

80 60 40 CO2 20

10

20

30

Time (sec) All figures created by Betsy Giaimo

Effects of Hematocrit on Human Blood Viscosity

Relative Viscosity

8

6

4

2

0.2

0.4 Hematocrit

0.6

0.8

Possible Explanation for Nocturia • Increased blood viscosity and arterial hypertension • Increased right ventricular afterload • Increased right ventricular end diastolic pressure and volume • Increased right atrial volume • Increased secretion of atrial natriuretic peptide from atrial myocytes, • Increases sodium excretion, and stretches receptors that suppress ADH secretion from the posterior pituitary gland

Effects of Arterial PO2 and PCO2 on Cerebral Blood Flow Arterial PCO2 (mm Hg) 20

40

60

80

100

20

40

60

80

100

Cerebral Blood Flow (ml/100mg/min)

100

75

50

25

Arterial PO2 (mm Hg)

Explanation for Morning Headaches • Hypoxia and hypercapnia during obstruction cause dilatation of cerebral blood vessels

CONDITIONS ASSOCIATED TO OSA

Signs of Obstructive Sleep Apnea • Systemic hypertension • Pulmonary hypertension (right axis deviation on ECG) • Polycythemia • Cor pulmonale • Bradycardia during apneic event • Tachycardia after airflow restored • Typically no respiratory abnormality while awake

Risk Factors

OSAS

Sex Age Obesity Smoking Alcohol

Cardiovascular Pathologies

Mechanisms for Cardiovascular Consequences of OSA

Arnardottir E et al, Sleep 32:447, 2009

Possible Explanation for Systemic Hypertension

• Repeated increases in sympathetic tone and systemic blood pressure during arousals may cause vascular remodeling and changes in endothelial function

OSAS & Arterial Hypertension Arterial hypertension is especially frequent in patients Suffering from OSAS Partisen M et Al. Sleep Res 1983;12:273 Kryger M et Al. WB Saunders 1989 Pekkarinen T et Al. Clin Endocrinol 1987; 27 649-654. Cozzi Fet Al Pediatrics 1985; 75:836-843 Bliwise D et Al Am J Public Haelth 1988:78:544-547

25 - 38%

OSAS = Indipendent risk for the Arterial Hypertension? Carlson J et Al Am J Respir Crit Care Med 1994;150:72-77 Fischer J et Al Pneumollogie 1993; 47 (Supl.1):151-154

Risk 2.1

Prospective Study of the Association between Sleep-Disordered Breathing and Hypertension Paul E. Peppard, Ph.D., Terry Young, Ph.D., Mari Palta, Ph.D., and James Skatrud, M.D. Volume 342:1378-1384 May 11, 2000 Number 19

NEJM Volume 342:1378-1384 May 11, 2000 N°19

Identifiable Causes of Hypertension 1° 1°

Sleep apnea Drug-induced or drug-related Chronic kidney disease Primary aldosteronism Renovascular disease Chronic steroid therapy and Cushing syndrome Pheochromocytoma Coarctation of the aorta Thyroid or parathyroid disease Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure:the JNC 7 rep. JAMA. 2003;289:2560-2572.

JAMA.October 8, 2003;290:1906-1914.

OSAS & Ischemic Cardiopathy

ECG ST elevation concomitant to apnoea induced Oxygen desaturation

Am. J. Respir. Crit. Care Med., Volume 164, Number 12, December 2001, 2147-2165 Sleep Apnea and Cardiovascular Disease Richard S. T. et Al

OSAS & Ischemic cardiopathy Snorers/Normal-- >Probability risk 2.3 D’Alessandro et Al. Br Med J 1990;300:1557-58

Apneics/Normal Heart failure risk in OSAS 23.3 times compared to normal subjects Hung J et Al Lancet 1990;336:261-264

OSAS & Ischemic Cardiopathy OSAS minimum prevalence among Coronaropathic subjects is about 16%

Andreas S et Al Coron Artery Dis 1996;7:541-545

62 patients with established CAD During the follow-up period (post-myocardial infarction), cardiovascular death occurred in six of 16 OSA patients (37.5%) compared with 4 (9.3%) in the non-OSA group (p = 0.018) Peker Y, et Al Am J Respir Crit Care Med. 2000;162:81-86

OSA is represents a risk factor for death in post-yocardial infarction

Systematic Revision JAMA. 2003;290:1906-1914 Obstructive Sleep Apnea Implications for Cardiac and Vascular Disease Abu S. M. Shamsuzzaman, et Al

The post-MI changes of cardiac function may predispose to the development of OSA, or may affect OSA severity.

Effects of Obstruction on Pulmonary Circulation and Right Ventricle • Hypoxic and hypercapnic pulmonary vasoconstriction cause pulmonary hypertension • Chronic nighttime hypoxia may cause erythropoiesis and polycythemia • Increased hematocrit increases blood viscosity • Hypoxic pulmonary vasoconstriction (HPV), increased blood viscosity, pulmonary hypertension increase right ventricular afterload • Increased right ventricular afterload may lead to right ventricular hypertrophy and eventually cor pulmonale

Possible Explanations for Bradycardia During Obstruction, Tachycardia after Airflow Restored • Stimulation of arterial chemoreceptors usually increases heart rate because it increases tidal volume (lung inflation reflex) • Stimulation of arterial chemoreceptors without stretching the lungs causes bradycardia • After arousal leads to restoration of airflow, large tidal volumes stretch lungs and cause tachycardia • May hyperventilate immediately after arousal, then hypoventilate until CO2 is restored

Artrial Fibrillation Ventricular Extrasystole Cardiaco arrest Sinus bradycardia Atrioventricular block Benefit of Atrial Pacing in Sleep Apnea Syndrome Stephane Garrigue, M.D. et Al NEJM Volume 346:404-412 February 7, 2002 Number 6

Cardiac arrhythmias, snoring, and sleep apnea V Hoffstein and S Mateika Department of Medicine, St. Michael's Hospital, Toronto, Canada.

458 patients . 82 % of patients with mean nocturnal oxygen saturation < 90 % had arrhythmias vs 40 % of patients with mean nocturnal oxygen saturation > 90 % 70 % of patients with AHI > 40 had arrhythmias vs 42% with AHI < or 40

Sleep-disordered breathing and cardiovascular disease: cross-sectional results of the Sleep Heart Health Study Shahar E, Whitney CW, Redline S, et al. Am J Respir Crit Care Med. 2001;163:19-25

“modest to moderate effects of sleep-disordered breathing on CVD manifestations within a range of the AHI that is typically considered "normal" or only mildly elevated (1-10 respiratory events per hour of sleep)”

Sleep-disordered breathing and cardiovascular disease: cross-sectional results of the Sleep Heart Health Study Shahar E, Whitney CW, Redline S, et al. Am J Respir Crit Care Med. 2001;163:19-25

modestly elevated risk coupled with a high prevalence of mild sleep-disordered breathing might have considerable public health implications

OSAS & Cerebral vascular pathology Snorers/controls stroke risk= 1.7-3.4 Partinen et Al Lancet 1985;8468:1325-1326 Palomaki et Al Stroke 1991; 22:1021-1025 Spriggs et Al Q J Med 1992;83: 555-562 Smirne S Eur et Al Respir J 1993; 6:1357-1361 Neau J et Al Acta Neurol Scand 1995;92: 63-68

However, it remains unclear whether sleep apnea is an independent risk factor for cerebrovascular disease.

Mortality and apnea index in obstructive sleep apnea. Experience in 385 male patients. He J, Kryger MH, Zorick FJ, Conway W, Roth T. Chest. 1988 Jul;94(1):9-14. 385 male OSA patients Probability of cumulative eight-year survival was 96 +/- 0.02 (SE) for HAI = less than 20 vs 63 +/- 0.17 for AHI greater than 20

EFFECTS of OSAS TREATMENT ON OSAS-RELATED CARDIOCIRCULATORY DISEASES

Refractory hypertension and sleep apnoea: effect of CPAP on blood pressure and baroreflex. Logan AG Et Al Eur Respir Journal 2003 Feb;21(2):241-7.

11.0 +/- 4.4 mmHg reduction in 24-h systolic BP 7.8 +/- 3.0 mmHg reduction in nightime diastolic BP

Pepperell JC,, et al. Ambulatory blood pressure after therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnoea: a randomised parallel trial. Lancet. 2002;359:204-210 Becker HF, Jerrentrup A, Ploch T, et al. Effect of nasal continuous positive airway pressure treatment on blood pressure in patients with obstructive sleep apnea. Circulation. 2003;107:68-73

“several months of CPAP therapy resulted in a small but significant reduction of daytime blood pressure of between 1.3 and 5.3 mm Hg”

Nocturnal ischemic events in patients with obstructive sleep apnea syndrome and ischemic heart disease: effects of continuous positive air pressure treatment. Peled N, Abinader EG, Pillar G, Sharif D, Lavie Am Coll Cardiol. 1999 Nov 15;34(6):1744-9

Treatment with continuous positive airway pressure significantly ameliorated the nocturnal ST depression time from 78 min to 33 min (p100 million

Global Alliance against Chronic Respiratory Diseases www.who.int/respiratory/gard

How common is OSA? • US study in 1993: 24% of men and 9% of women had AHI>5 (age 30-60) • 4% of men and 2% of women reported daytime sleepiness also (OSAS) • UK study in 1991: 1% of men had OSAS • Prevalence likely to increase as obesity level rises

Ferini-Strambi L et al, 2004 • Minimally symptomatic or asymptomatic OSA is estimated to occur in 1 of 5 adults • OSA with daytime impairment (OSA syndrome) occur in 1 of 20 adults and is rarely recognized

Symptoms attributed to sleep apnea ranked in order of frequency selected

Questionnaries Epworth Sleepiness Scale

Limited utily of ESS and other sleepines scales to predict the presence of OSAS

Clinical Impressions Upper airways abnormalities High-arched palate Large tonghe Tonsillar hypertrophy Redundant soft palatal tissue Retrognathia Micrognathia Allergic Rhinitis Features Morphometric measurements Measuring neck size Performing skin fold thickness measurements

Assessment of the Upper Airways

Direct visualisation Endoscopy Rhinometry Rhinomanometry Imaging

Clinical Impressions History + Physical examination: sensitivity 50% Hoffstein & Szalai Sleep 1993

Bed partner report of apnea an snoring: Sensitivity 78% Specificity 64% Positive predictive value 64% Kapuniai et al Sleep 1988

Integration of Multiple Factors Witnessed apnea Snoring Nocturnal choking Excessive daytime sleepiness Motor vehicle accidents Male sex Obesity Hypertension

80%

American Sleep Disorders Association, 1994 Level I

Level II

Parameters

> 7, EEG, EOG, EMG chin, ECG, flow, respiratory effort, SaO2

> 7, EEG, EOG, EMG chin, ECG, flow, respiratory effort, SaO2

> 4, including Minimum of ventilation (at one least two channels of respiratory activity)

Body Position

Documented or objectively measured In costant attendance

May be objectively measured

May be objectively measured

Not measured

Not in attendance

Not in attendance

Not in attendance

Personnel

Interventions Possible

Level III

Not possible Not possible

Level IV

Not possible

Ossimetria Holter

Flow evaluation

Flow evaluation

Flow evaluation

Level I

Level II

Parameters

> 7, EEG, EOG, EMG chin, ECG, flow, respiratory effort, SaO2

> 7, EEG, EOG, EMG chin, ECG, flow, respiratory effort, SaO2

> 4, including Minimum of ventilation (at one least two channels of respiratory activity)

Body Position

Documented or objectively measured In costant attendance

May be objectively measured

May be objectively measured

Not measured

Not in attendance

Not in attendance

Not in attendance

Personnel

Interventions Possible

Level III

Not possible Not possible

Level IV

Not possible

Microphone Flow sensor (or PneumoFlow®)

Body position sensor with integrated thoracic sensor

ECG electrodes

Abdominal sensor

Oxygen saturation sensor

Activity sensor Pressure sensor

VALIDATION STUDIES • Esnaola S et al, Eur Respir J 1996 (MesamIV) • Zucconi M et al, Eur Respir J 1996 (MicroDigitrapper)

• Ficker JH et al, Respiration 2001 (Somnocheck)

⇒ The diagnostic accuracy of manual analysis was found to be superior to that of automatic analysis

Level I

Level II

Parameters

> 7, EEG, EOG, EMG chin, ECG, flow, respiratory effort, SaO2

> 7, EEG, EOG, EMG chin, ECG, flow, respiratory effort, SaO2

> 4, including Minimum of ventilation (at one least two channels of respiratory activity)

Body Position

Documented or objectively measured In costant attendance

May be objectively measured

May be objectively measured

Not measured

Not in attendance

Not in attendance

Not in attendance

Possible

Not possible Not possible

Personnel Interventions

Level III

Level IV

Not possible

Management Options in OSAS Subjective Indicators:

• Sleepiness. • Quality of life • Mood • Symptoms • Work

Objective Indicators:

• Comorbidity: (Cardiovascular and Respiratory diseases, Hypertension )

• Neuropsychiatric and behavioral complications

• AHI, ODI, RDI

CPAP for OSAS

• AHI >20 with or without symptoms • AHI 5-19 with complications

sleepiness,

behavioral

Modified ACCP Statement

TREATMENT • AHI > 25 and severe clinics • AHI < 25 and mild clinics • AHI < 25 and severe clinics

nCPAP + sleep hygiene

• AHI > 25, mild clinics • Alterations of soft tissues or of the scheleton

Sleep hygiene and diet

Sleep hygiene and diet Sleep hygiene , diet and temporary nCPAP

Surgery, especially in young and/or non obese patients

Lack of efficacy for a cervicomandibular support collar in the management of obstructive sleep apnea Skinner et al, CHEST 2004

AIM: To bring the mandibule ahead

Management Options in OSAS Nasal Continuous Positive Airway Pressure Therapy

CPAP provides a splint

Upper airway dilator muscle activity Hypoxemia

Splinting of upper airway suction pressure

Diaphragm efficiency

Nasal CPAP

end expiratory lung volume

Splinting of upper airway

Excessive daytime sleepness

Upper airway collapse

Pharyngeal crosssectional area

Upper airway mucosal Edema

snoring

60

RDI

P

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